Education

1967      Ph.D. Medicinal Chem., Univ. of Kansas

1960      B.Ph.Chem. University of Cairo

1967-69 Postdoctoral Fellow, U.C. Berkeley

Honors & Awards

2002      Achievement Award, Drug Design & Discovery, AAPS

2006      Lifetime Achievement Award, ICRS

2006      UCONN Inventor’s Awards

Research Interests
The Endocannabinoid System in Drug Discovery:  Cannabinergic drugs modulate the central nervous and immune systems by acting through two receptors (CB1; CB2) and two classes of endogenous ligands represented by anandamide and 2-arachidonyl glycerol (endocannabinoids).  The endocannabinoid system is further regulated by two inactivating enzymes, fatty acid amide hydrolase (FAAH) and Monoacyl glycerol lipase (MGL), and a newly discovered transport system.  We are studying the interactions of cannabinergic ligands with the above receptors, enzymes and transporters using a combination of chemical, biochemical, biophysical and computational methods.  The use of NMR and mass spectroscopy are emphasized.  Our results are used to design and synthesize novel therapeutically useful drugs for pain, appetite and central nervous system diseases.

Interactions of Drugs with Membranes: We study the effects of drug molecules on membranes using solution and solid-state nuclear magnetic resonance and computational methods and use the results to design and synthesize improved medications. The classes of drugs include cannabinoids, steroids and antineoplastic ether lipids. The work also includes studying the mechanism by which these molecules are transported across the blood brain barrier.

Our research is well supported by NIH grants and offers opportunities for training in model medicinal chemistry.  Choices of projects within the Center for Drug Discovery include: a) drug design and synthesis; b) chemical/biochemical approaches for studying drug:receptor interactions and; c) the role of membranes in drug action using biophysical methods.

Selected Publications

Ibrahim, M.M., Porreca, F., Lai, J., Albrecht, P.J., Rice, F.L., Khodorova, A., Davar, G., Makriyannis, A., Vanderah, R.W., Mata, H.P. and Malan, T.P., CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids, Proc. Natl. Acad. Sci. U.S.A., 102 (2005) 3093-3098.

Li, C., Wei, X., Vadivel, S.K. and Makriyannis, A., High affinity electrophilic and photoactivatable covalent endocannabinoid probes for the CB1 receptor., J. Med. Chem., 48 (2005) 6423-9.

Tian, X., Guo, J., Yao, F., Yang, D.P. and Makriyannis, A., The conformation, location, and dynamic properties of the endocannabinoid ligand anandamide in a membrane bilayer, J. Biol. Chem., 280 (2005) 29788-95.